My long term professional goals are to improve the understanding of the link between substance misuse and intimate partner violence (IPV), to enhance treatment options available, and to serve as a role model and mentor to the next generation of patient-oriented alcohol researchers. My goal is to have protected time to spend focused effort on mentoring at least 10 faculty mentees, including at minimum, one NIAAA-funded K01 award recipient, one NICHD-funded K23 recipient, one NIAAA-funded F-32 recipient, and 7 additional assistant or associate professors who have recently or are in the process of applying for external funding. For my own career development I would like to conduct multidisciplinary research and learn the necessary skills to expand my program of research to the genetics of alcohol treatment and aggression. This will involve obtaining training in molecular genetics, advanced statistical modeling of genetic variants influencing human behavior and psychiatric conditions, and focused attention on the ethical ramifications of conducting genetics research. IPV results in devastating consequences, including physical and mental health problems, divorce, suicide, and spousal homicide. There is substantial evidence for the association between alcohol use and IPV. Recent research has shown that IPV perpetration and victimization by both genders is 5-20 times more likely to occur on a drinking day than on a non-drinking day. In populations of individuals with alcohol problems, research has shown that extended interventions specifically designed to reduce alcohol use also produce decreases in IPV. However, research suggests that treatment for IPV among individuals arrested for domestic violence is relatively ineffective, particularly among individuals who use alcohol excessively. Batterer treatment outcome research has shown that men with alcohol problems are 16 times more likely to recidivate to violence after the intervention than men without alcohol problems. To date, there is minimal research on the extent to which treatment for hazardous alcohol use will ameliorate subsequent IPV in batterers. I am currently conducting two randomized clinical trials wherein male and female hazardous drinkers who have been arrested for domestic violence and court-referred to batterer intervention programs are assigned to either a brief, motivationally focused alcohol intervention plus standard batterer intervention or standard batterer intervention alone. Alcohol use, problems arising from alcohol use, and physical, sexual, and psychological aggression are assessed at baseline, 3-, 6-, and 12-month follow-up. Arrest records and protection orders are obtained as further indices of violence recidivism. We hypothesize that adding a brief alcohol treatment to standard batterer intervention will result in less alcohol use and IPV perpetration and victimization at follow-up, relative to standard care alone. To date, our findings support these hypotheses. These grants focus on the incremental efficacy of a brief alcohol intervention in reducing alcohol use and by extension intimate partner violence (IPV), including the identification of moderators of the interventions. In this K24 application, I seek support for genotyping empirically-supported candidate genes in biologically driven pathways and using an aggregate genetic risk score (AGRS) approach to examining genetic associations with alcohol-related phenotypes (including treatment response) as well as IPV-related phenotypes over time. Research participants will be recruited from my ongoing randomized clinical trials. This proposed K24 award affords an excellent opportunity to improve our knowledge base regarding the association between genes, IPV, and alcohol and violence treatment outcome. I propose to collect and analyze DNA from a minimum of 175-200 male batterer participants and at least 175-200 arrested women participants to examine the role of empirically selected candidate genes in association with phenotypes of aggression and alcohol treatment response. We will examine whether aggregate genetic risk scores derived from empirically- selected candidate polymorphisms in the dopaminergic and serotonergic systems are associated with the frequency and severity of IPV, and substance use, at baseline and over time. We will also examine whether GABRA2 polymorphisms and haplotypes are associated with IPV and alcohol treatment outcome. For exploratory purposes, we will investigate whether gender differences emerge in genetic models, and whether sex-linked variation in the MAO-A gene is associated with IPV perpetration over time. Knowledge regarding genetic predictors of violence and substance use treatment outcomes could advance theoretical models of substance use and aggression and could ultimately be used for patient-treatment matching. Results will significantly contribute to our understanding of the biological underpinnings of these societal problems, and may suggest immediate translational benefits to targeting behavioral interventions by genetic background. Banking the DNA samples will allow us to examine other candidate genes as their relevance emerges in the literature. Identifying the role of genetics in alcohol use and aggressive behavior will facilitate the development of more robust treatments and prevention strategies. The proposed K24 award will provide the protected time required to cultivate my knowledge of behavioral genetics research, while allowing me considerable time to mentor an outstanding group of junior colleagues.